Optimization of Thermoreversible In Situ Nasal Gel of Timolol Maleate.

Nasal route had shown better systemic bioavailability due to its large surface area, porous endothelial membrane, high total blood flow, and avoidance of first-pass metabolism. Timolol maleate is a beta blocker used primarily in the treatment of hypertension. Drug undergoes extensive hepatic first-pass metabolism (80%). The drug has half-life of 4 hrs. Oral bioavailability of timolol maleate is 61%. The aim of the present study was to optimize controlled release in situ nasal delivery for timolol maleate. HPMC and Poloxamer 407 were selected as polymer in formulation of thermoreversible in situ nasal gel. Optimization was carried out using 3(2) factorial design. It was observed that formulations f1 and f4 revealed the highest % drug release, that is, 93.57% and 91.66%, respectively. Factorial design study indicated that the drug release and viscosity were most significant dependent factors. Ex vivo diffusion study through nasal mucosa indicated 67.26 ± 2.10% and 61.07 ± 2.49% drug release for f1 and f4 formulations. f1 was the optimized batch. This batch thus can act as a potential nasal delivery with enhanced bioavailability for the drug.

Bioactive thermoresponsive polyblend nanofiber formulations for wound healing.

The rationale of this work is to develop new bioactive thermoresponsive polyblend nanofiber formulations for wound healing (topical). Various polymer compositions of thermoresponsive, poly(N-isopropylacrylamide), egg albumen and poly(ε-caprolactone) blend solutions with and without a drug [gatifloxacin hydrochloride, Gati] were prepared. Non-woven nanofibers of various compositions were fabricated using an electrospinning technique. The morphology of the nanofibers was analyzed by an environmental scanning electron microscope. The morphology was influenced by the concentration of polymer, drug, and polymer blend composition. Fourier transform infrared spectroscopy analysis showed the shift in bands due to hydrogen ion interactions between polymers and drug. Thermogram of PNIPAM/PCL/EA with Gati recorded a shift in lower critical solution temperature (LCST) and glass transition temperature (Tg) of PNIPAM. Similarly Tg and melting temperature (Tm) of PCL were shifted. X-ray diffraction patterns recorded a decrease in the crystalline state of PCL nanofibers and transformed crystalline drug to an amorphous state. In vitro release study of nanofibers with Gati showed initial rapid release up to 10h, followed by slow and controlled release for 696h (29days). Nanofiber mats with Gati exhibited antibacterial properties to Staphylococcus aureus, supported suitable controlled drug release with in vitro cell viability and in vivo wound healing.

Design and evaluation of polyox and pluronic controlled gastroretentive delivery of troxipide.

Objective. Objective of the present work was to develop site-specific gastroretentive drug delivery of Troxipide using polymers Pluronic F127 and Polyox 205 WSR. Troxipide is a novel gastroprotective agent with antiulcer, anti-inflammatory, and mucus secreting properties with elimination half-life of 7.4 hrs. Troxipide inhibits H. pylori-derived urease. It is mainly absorbed from stomach. Methods. 3(2) factorial design was applied to study the effect of independent variable. Effects of concentration of polymer on dependant variables as swelling index, hardness, and % drug release were studied. Pluronic F127 and Polyox 205 WSR were used as rate controlled polymer. Sodium bicarbonate and citric acid were used as effervescent-generating agent. Results. From the factorial batches, it was observed that formulation F5 (19% Pluronic F127 and 80% Polyox 205 WSR) showed optimum controlled drug release (98.60% ± 1.82) for 10 hrs with ability to float >12 hrs. Optimized formulation characterized by FTIR and DSC studies confirmed no chemical interactions between drug and polymer. Gastroretention for 6 hrs for optimized formulations was confirmed by in vivo X-ray placebo study. Conclusion. Results demonstrated feasibility of Troxipide in the development of gastroretentive site-specific drug delivery.

Development of press-coated, floating-pulsatile drug delivery of lisinopril.

Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor, primarily used for the treatment of hypertension, congestive heart failure, and heart attack. It belongs to BCS class III having a half-life of 12 hrs and 25% bioavailability. The purpose of the present work was to develop a press-coated, floating-pulsatile drug delivery system. The core tablet was formulated using the super-disintegrants crosprovidone and croscarmellose sodium. A press-coated tablet (barrier layer) contained the polymer carrageenan, xanthan gum, HPMC K4M, and HPMC K15M. The buoyant layer was optimized with HPMC K100M, sodium bicarbonate, and citric acid. The tablets were evaluated for physical characteristics, floating lag time, swelling index, FTIR, DSC, and in vitro and in vivo behavior. The 5% superdisintgrant showed good results. The FTIR and DSC study predicted no chemical interactions between the drug and excipients. The formulation containing xanthan gum showed drug retaining abilities, but failed to float. The tablet containing HPMC K15M showed a high swelling index. The lag time for the tablet coated with 200 mg carrageenan was 3±0.1 hrs with 99.99±1.5% drug release; with 140 mg HPMC K4M, the lag time was 3±0.1 hrs with 99.71±1.2% drug release; and with 120 mg HPMC K15M, the lag time was 3±0.2 hrs with 99.98±1.7% drug release. The release mechanism of the tablet followed the Korsmeyer-Peppas equation and a first-order release pattern. Floating and lag time behavior have shown good in vitro and in vivo correlations.

Optimization studies on compression coated floating-pulsatile drug delivery of bisoprolol.

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 3² full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form.

Application of design of experiment for floating drug delivery of tapentadol hydrochloride.

The aim of the present study was to apply design of experiment (DOE) to optimize floating drug delivery of tapentadol hydrochloride. Tapentadol hydrochloride is a synthetic opioid used as a centrally acting analgesic and effective in both experimental and clinical pain. The half-life of the drug is about 4 hours and oral dose is 50 to 250 mg twice a day. For optimization 3(2) full factorial design was employed for formulation of tapentadol hydrochloride tablets. Sodium bicarbonate was incorporated as a gas-generating agent. Combination of polymers Xanthan gum and Locust bean gum was used to achieve controlled release effect. The concentration of polymers was considered as the independent variables and dependent variables were floating lag time and swelling index of the tablets. From the factorial batches, it was observed that formulation containing combination of 20% sodium bicarbonate and 10% citric acid shows optimum floating ability whereas the formulation containing 20% Xanthan gum and 28% Locust bean gum shows optimum sustained drug release pattern with adequate floating.

Formulation, development, and evaluation of floating pulsatile drug delivery system of atenolol.

The objective of this work was to develop and evaluate a floating-pulsatile drug delivery of atenolol. The floating-pulsatile concept was applied to increase the gastric residence of the dosage form by having lag phase followed by a burst release. The system was generated which consisted of three different parts: a core tablet, containing the active ingredient; an erodible outer shell; and a top cover buoyant layer. The dry, coated tablet consists in a drug-containing core, coated by a hydrophilic erodible polymer responsible for a lag phase in the onset of pulsatile release. The buoyant layer, prepared with hydroxypropyl methylcellulose (HPMC) K100 M, citric acid, and sodium bicarbonate, provides buoyancy to increase the retention of the oral dosage form in the stomach. The effect of the hydrophilic erodible polymer characteristics on the lag time and drug release was investigated. Developed formulations were evaluated for their physical properties in vitro release as well as in vivo behavior. The results showed that K3 (180 mg of HPMC K4 M) and K6 (290 mg of HPMC E15 LV) with a buoyant layer were the best formulation, with lag times of 5.2 ± 0.1 h and 4.1 ± 0.2 h, respectively. Floating time was controlled by the quantity and composition of the buoyant layer. In-vitro results point out the capability of the system with its prolonged residence of the tablets in the stomach and release of drug after a programmed lag time. This was confirmed by in vivo x-ray technique. LAY ABSTRACT: The objective of the present work was to develop a floating-pulsatile oral drug delivery system of atenolol with addition of hydroxylpropyl methylcellulose (HPMC) K100 M, HPMC K4 M, and HPMC E15 LV in different ratios with citric acid and sodium bicarbonate as gas-forming agents. The system consist of three different parts: a core tablet, containing the active ingredient; a bottom layer that erodes; and a top cover floating layer. Atenolol, a ß-blocker, is prescribed widely in diverse cardiovascular diseases, for example, hypertension, angina pectoris, arrhythmias, and myocardial infarction. Developed formulations were evaluated for their physical properties and vitro release as well as in vivo behavior. The results showed that K3 (180 mg HPMC K4 M) and K6 (290 mg of HPMC E15 LV) with a buoyant layer were the best formulations with the lag times of 5.2 ± 0.1 h and 4.1 ± 0.2 h, respectively, and were found to be the best choice for manufacturing tablets.

Application of design of experiments to optimizing novel gastroretentive drug delivery of simvastatin.

CONTEXT: Simvastatin is a hypolipidemic drug used in atherosclerosis. It has short elimination half life (2-3 hours) and narrow absorption window. It is mainly absorbed from stomach. OBJECTIVE: The objective of this research was to develop gastroretentive floating tablets of Simvastatin using combination of release retardant polymers like Polyox WSR 205, Polyox WSR N12K and HPMC K4M. MATERIAL AND METHODS: 3(2) full Factorial design was applied to design the experiments and tablets were prepared by direct compression. Prepared floating tablets were evaluated for hardness, floating time, friability, % drug content, swelling index, in-vitro drug release study and mean gastric retention period by invivo X-ray study. Statistical analysis was done using design expert software and model fitting was carried out using PCP DISSO. Design expert software was validated by comparing predicted results with observed results. RESULTS AND CONCLUSION: Statistical analysis data revealed that tablets from formulation batch D3 (containing HPMC K4M 10% and POLYOX WSR 205 35%) and formulation batch E2 (HPMC K4M 10% and Polyox WSR N12K 25%) were promising system exhibiting excellent floating properties and drug release pattern. Stability studies revealed that all formulations were physically and chemically stable. In-vivo X-ray imaging of formula D3 and formula E2 shows mean gastric retention time of 6 ± 0.5 hours.

Dissolution Rate Enhancement, Design and Development of Buccal Drug Delivery of Darifenacin Hydroxypropyl ß-Cyclodextrin Inclusion Complexes.

Darifenacin is a urinary antispasmodic. The oral absorption of darifenacin is poor due to its low solubility and poor bioavailability (15-19%). Darifenacin was complexed with hydroxylropyl beta-cyclodextrin (Hpß-CD). The best results were obtained with the coevaporation that interacts in a 1 : 1 drug : cyclodextrin molar ratio. The solid inclusion complexes were found to be amorphous in the characterization. The dissolution rate of darifenacin from the Hpß-CD solid inclusion complex was increased compared to the powdered drug. The controlled release buccoadhesive patches for the delivery of darifenacin were prepared using HPMC K100M CR and HPMC K15. The coevaporation complex of the drug was used in the formulation due to its increased saturation solubility and increased ease of dissolution. The patches were evaluated for their surface pH, folding endurance, swelling, mucoadhesive properties, in vitro residence time, vapour transmission test, and in vitro and ex vivo release studies. Formulations Hb2 (2%) and Pb4 (4%) were found to be optimized. These two formulations can be used for buccal delivery of darifenacin which avoids first pass effect and leads to increased bioavailability of darifenacin.

Solubility enhancement, physicochemical characterization and formulation of fast-dissolving tablet of nifedipine-betacyclodextrin complexes

The main objective of the study was to enhance the dissolution of nifedipine, a poorly water soluble drug by betacyclodextrin complexation and to study the effect of the preparation method on the in vitro dissolution profile. The stoichiometric ratio determined by phase solubility analysis for inclusion complexation of nifedipine with β-cyclodextrin was 1:1. Binary complex was prepared by different methods and was further characterized using XRD, DSC and FT-IR. A saturation solubility study was carried out to evaluate the increase in solubility of nifedipine. The optimized complex was formulated into fast-dissolving tablets by using the superdisintegrants Doshion P544, pregelatinized starch, crospovidone, sodium starch glycolate and croscarmellose sodium by direct compression. Tablets were evaluated for friability, hardness, weight variation, disintegration and in vitro dissolution. Tablets showed an enhanced dissolution rate compared to pure nifedipine.

Este estudo teve por objetivo principal incrementar a dissolução do nifedipino, fármaco pouco solúvel em água, por meio de sua complexação com β-ciclodextrina e estudar o efeito do método de preparação sobre o perfil de dissolução in vitro. A razão estequiométrica, determinada por ensaio de solubilidade de fase, para a complexação de nifedipino por inclusão em β-ciclodextrina foi 1:1. O complexo binário foi preparado por diferentes métodos, sendo caracterizado utilizando-se difratometria de raios X (XRD), calorimetria diferencial de varredura (DSC) e espectroscopia no infravermelho com transformada de Fourier (FT-IR). Realizou-se estudo de solubilidade de saturação para avaliar o incremento da solubilidade do nifedipino. O complexo otimizado foi formulado em comprimidos de dissolução rápida preparados por compressão direta, nos quais se utilizaram os superdesintegrantes Doshion P544, amido pré-gelatinizado, crospovidona, amidoglicolato de sódio e croscarmelose sódica. Os comprimidos, que foram avaliados quanto à friabilidade, dureza, variação de peso, desintegração e dissolução in vitro, apresentaram taxa de dissolução superior à do nifedipino pura.

Development and validation of a stability indicating RP-HPLC method for simultaneous estimation of Olmesartan Medoxomil and Metoprolol Succinate in pharmaceutical dosage form.

AIM AND BACKGROUND: A simple, rapid, precise and isocratic RP-HPLC (Reverse Phase High Performance Liquid Chromatography) method is aimed to develop for the simultaneous estimation of Olmesartan Medoxomil and Metoprolol Succinate in bulk drug and pharmaceutical dosage form. MATERIALS AND METHODS: The quantification is carried out using YMC-Pack CN (250 × 4.6 mm, 5.0 µm) column and the mobile phase comprises of 0.05% Trifluoro acetic acid (TFA) and Acetonitrile (ACN) (70:30 v/v). The flow rate is 1.0 ml/min. The eluent is monitored at 220 nm. The retention times of Olmesartan Medoxomil and Metoprolol Succinate are 7.9 min and 4.1 min respectively. The method is validated in terms of linearity, precision, accuracy, specificity, limit of detection and limit of quantitation. RESULTS: Linearity and percentage recoveries of both Olmesartan Medoxomil and Metoprolol Succinate are in the range of 5-35 µg/ml and 100 ± 2%, respectively. The stress testing of both the drugs individually and their mixture is carried out under acidic, alkaline, oxidation, photo-stability and thermal degradation (dry heat and wet heat) conditions and its degradation products are well resolved from the analyte peaks. CONCLUSION: This method was successfully validated for accuracy, precision, and linearity.

Physicochemical characterization and solubility enhancement studies of allopurinol solid dispersions / Caracterização físico-química e estudos de solubilidade de melhoria de dispersões sólidas de alopurinol

Allopurinol is a commonly used drug in the treatment of chronic gout or hyperuricaemia associated with treatment of diuretic conditions. One of the major problems with the drug is that it is practically insoluble in water, which results in poor bioavailability after oral administration. In the present study, solid dispersions of allopurinol were prepared by solvent evaporation, kneading method, co-precipitation method, co-grinding method and closed melting methods to increase its water solubility. Hydrophilic carriers such as polyvinylpyrrolidone, polyethylene glycol 6000 were used in the ratio of 1:1, 1:2 and 1:4 (drug to carrier ratio). The aqueous solubility of allopurinol was favored by the presence of both polymers. These new formulations were characterized in the liquid state by phase solubility studies and in the solid state by differential scanning calorimetry, powder X-ray diffraction, UV and Fourier Transform Infrared spectroscopy. Solid state characterizations indicated that allopurinol was present as an amorphous material and entrapped in polymer matrix. In contrast to the very slow dissolution rate of pure allopurinol, the dispersion of the drug in the polymers considerably enhanced the dissolution rate. Solid dispersion prepared with polyvinylpyrrolidone showed highest improvement in wettability and dissolution rate of allopurinol. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Non-Fickian diffusion. Therefore, the present study showed that polyvinylpyrrolidone and polyethylene glycol 6000 have a significant solubilizing effect on allopurinol.

Alopurinol é fármaco comumente utilizado no tratamento de gota crônica ou hiperuricemia associada com o tratamento em condições diuréticas. Um dos maiores problemas com o fármaco é que este é praticamente insolúvel em água, o que resulta em baixa biodisponibilidade na administração oral. No presente estudo, dispersões sólidas de alopurinol foram preparadas pela evaporação do solvente, pelos métodos de amassamento, de coprecipitação, de comoagem e fusão fechada para aumentar sua solubilidade em água. Transportadores hidrofílicos, como polivinilpirrolidona, polietilenoglicol 6000 foram utilizados nas proporções de 1:1. 1:2 e 1:4 (fármaco: transportador). A solubilidade aquosa do alopurinol foi favorecida pela presença de ambos os polímeros. Estas novas formulações forma caracterizadas no estado líquido pelos estudos de solubilidade de fase e no estado sólido pela calorimetria diferencial de varredura, difração de Raio-X, espectroscopia de UV e de IV com transformada de Fourier. As caracterizações do estado sólido indicaram que o alopurinol estava presente como material amorfo e embebido em matriz polimérica. Ao contrário da velocidade de dissolução lenta do alopurinol puro, a dispersão do fármaco nos polímeros aumentou consideravelmente a taxa de dissolução. A dispersão sólida preparada com polivinilpirrolidona mostrou as maiores melhorias na molhabilidade e taxa de dissolução do alopurinol. A modelagem matemática dos dados da dissolução in vitro indicou o melhor ajuste ao modelo de Korsemeyer-Peppas e a cinética de liberação do fármaco primariamente como difusão não-Fickiana. Assim, o presente estudo mostrou que a polivinilpirrolidona e o polietilenoglicol 6000 têm efeito significativo na solubilização do alopurinol.

Pulsatile multiparticulate drug delivery system for metoprolol succinate.

Cardiovascular diseases and their treatment pose a great challenge. Many instances of cardiovascular disease occur in the early morning hours. Hence, the objective of this study was to develop a time-controlled release formulation of metoprolol succinate based on a pulsatile multiparticulate (pellets) drug delivery system. The formulation was intended to be administered in the evening at 22:00 hours to evaluate symptoms of cardiovascular disease that are experienced in the early morning hours (from 04:00 to 06:00). Drug layering followed by a swelling layer and finally by an insoluble coat application was done using a Sanmour fluid bed processor. Metoprolol succinate layered on sugar pellets (74% w/w) layered with 20% (w/w) ion doshion resin P-547 and coated with 15% (w/w) ethocel with the addition of 20% castor oil showed a lag time of 4 h and was then followed a sigmoidal release pattern with more than 95% drug having been released by the 10(th) h.

Development and validation of a HPTLC method for simultaneous estimation of lornoxicam and thiocolchicoside in combined dosage form.

AIM: To develop a simple, precise, rapid and accurate HPTLC method for the simultaneous estimation of Lornoxicam (LOR) and Thiocolchicoside (THIO) in bulk and pharmaceutical dosage forms. MATERIALS AND METHODS: The separation of the active compounds from pharmaceutical dosage form was carried out using methanol:chloroform:water (9.6:0.2:0.2 v/v/v) as the mobile phase and no immiscibility issues were found. The densitometric scanning was carried out at 377 nm. The method was validated for linearity, accuracy, precision, LOD (Limit of Detection), LOQ (Limit of Quantification), robustness and specificity. RESULTS: The Rf values (±SD) were found to be 0.84 ± 0.05 for LOR and 0.58 ± 0.05 for THIO. Linearity was obtained in the range of 60-360 ng/band for LOR and 30-180 ng/band for THIO with correlation coefficients r(2) = 0.998 and 0.999, respectively. The percentage recovery for both the analytes was in the range of 98.7-101.2 %. CONCLUSION: The proposed method was optimized and validated as per the ICH guidelines.

Development and validation of UV-Visible spectrophotometric baseline manipulation methodology for simultaneous analysis of drotraverine and etoricoxib in pharmaceutical dosage forms.

INTRODUCTION: A simple, economical, precise, and accurate new UV spectrophotometric baseline manipulation methodology for simultaneous determination of drotaverine (DRT) and etoricoxib (ETR) in a combined tablet dosage form has been developed. MATERIALS AND METHODS: The method is based on baseline manipulation (difference) spectroscopy where the amplitudes at 274 and 351 nm were selected to determine ETR and DRT, respectively, in combined formulation and methanol was used as solvent. Both the drugs obey Beer's law in the concentration ranges of 4-20 µg/mL for DRT and 4.5-22.5 µg/mL for ETR. RESULTS: The results of analysis have been validated statistically and recovery studies confirmed the accuracy and reproducibility of the proposed method which were carried out by following the ICH guidelines. CONCLUSION: It has been concluded that a new simple and accurate UV spectrophotometric baseline manipulation method was developed for simultaneous do not declare DRT and ETR in a combined tablet dosage form has been developed.

Formulation and in vitro evaluation of taste-masked oro-dispersible dosage form of diltiazem hydrochloride

Diltiazem hydrochloride is a calcium channel blocker generally indicated for the treatment of angina and hypertension, and it is extensively metabolized due to the hepatic metabolism. Formulation of diltiazem hydrochloride into an oro-dispersible dosage form can provide fast relief with higher bioavailability. The bitter taste of the drug should be masked to formulate it in a palatable form. In the present work, an attempt was made to mask the taste by complexation technique, with a formulation into an oro-dispersible dosage form, using superdisintegrants Doshion P544, crospovidone (CP) and sodium starch glycolate (SSG). The complexes of diltiazem hydrochloride with β-CD (1:1 molar ratio) were prepared by kneading, co-evaporation, co-grounding, freeze-drying and melting methods. Phase solubility showed stability constant 819.13M-1. Prepared inclusion complexes were evaluated for taste masking and characterized by I.R, XRD, DSC. Using the drug β-CD complex, oro-dispersible tablets were prepared and evaluated for hardness, friability, weight variation, thickness, disintegrating time (DT), dissolution rate and taste. Formulations with 4 percent Doshion, 8 percent CP and 4 percent SSG showed DT of 0.54, 0.35 and 1.23 minutes, respectively.

O cloridrato de diltiazem é bloqueador do canal de cálcio geralmente indicado para o tratamento de angina e de hipertensão e é extensamente biotransformado devido ao metabolismo hepático. A formulação do cloridrato de diltiazem em orodispersão pode prover rápida liberação com maior biodisponibilidade. O sabor amargo do fármaco deve ser mascarado para ser formulado em forma palatável. No presente trabalho tentou-se mascarar o sabor pela técnica de complexação, com uma orodispersão, usando superdesintegrantes, como Doshio P544, crospivodina (CP) e glicolato de amido sódico (SSG). Os complexos de cloridrato de diltiazem com β-CD (razão molar 1:1) foram preparados por mistura, coevaporação, comoagem, liofilização e métodos de fusão. A solubilidade de fase mostrou estabilidade constante de 819,13 M-1. Os complexos de inclusão preparados foram avaliados com relação ao mascaramento do sabor e caracterizados por IV, Difração de Raios X e DSC. Empregando-se o fármaco complexado com β-CD, prepararam-se comprimidos dispersíveis e avaliaram-se os mesmos quanto à dureza, friabilidade, variação de peso, espessura, tempo de desintegração (DT), taxa de dissolução e sabor. Formulações com 4 por cento de Doshion, 8 por cento de CP e 4 por cento de SSG mostraram DT de 0,54, 0,35 e 1,23 minutos, respectivamente.

Development and optimization of metoprolol succinate gastroretentive drug delivery system.

Metoprolol succinate (MS) gastroretentive (GR) controlled release system was formulated to increase gastric residence time leading to improved drug bioavailability. Box-Behnken model was followed using novel combinations of sodium alginate (SA), sodium carboxymethylcellulose (NaCMC), magnesium alumino metasilicate (MAS) as independent variables. Floating lag time (Flag), t25, t50, t75, diffusion exponent as dependent variables revealed that the amount of SA, NaCMC and MAS have a significant effect (p < 0.05) on t25, t50, t75 and Flag. MSGR tablets were prepared and evaluated for mass, thickness, hardness, friability, drug content and floating property. Tablets were studied for dissolution for 24 h and exhibited controlled release of MS with floating for 16 h. The release profile of the optimized batch MS01 fitted first-order kinetics (R2 = 0.9868, n = 0.543), indicating non-Fickian diffusion or anomalous transport by diffusion and swelling.

Superdisintegrant Selection for Tramadol Dispersible Tablets

The selection of a suitable superdisintegrant for a rapidly disintegrating dosage form is of the utmost importance, since disintegration time (DT) is a critical parameter. An experimental design was implemented, to find out the effects of superdisintegrants (sodium starch glycolate, crospovidone, croscarmellose sodium and methacrylic copolymer with divinyl benzene), at 2, 4, 6% w/w, on tablet hardness, with respect to DT. Methacrylic copolymer with divinyl benzene (at 4 wt%) was selected as the best superdisintegrant, adequate for the formulation of dispersible Tramadol tablets. With increasing hardness, there was a considerable increase in DT at all concentrations of superdisintegrants. A combination of crospovidone and methacrylic copolymer with divinyl benzene showed a remarkable drop in DT to 0.33 min. The stability of the batch with lowest DT was also tested under various conditions and the results suggested that there was no degradation over the test period.

Inhibitory effect of rutin and curcumin on experimentally-induced calcium oxalate urolithiasis in rats.

BACKGROUND: Renal epithelial cell injury by reactive oxygen species is pre-requisite step in the pathogenesis of urolithiasis. Rutin and curcumin are polyphenolic compounds known to have antioxidant and anti-inflammatory activities, but their effect on urolithiasis is yet to be elucidated. In the present study, we have investigated the inhibitory effect of rutin and curcumin on calcium oxalate urolithiasis in Wistar albino rats. METHODS: Calcium oxalate urolithiasis was induced experimentally by administration of 0.75% v/v ethylene glycol with 1% w/v ammonium chloride in drinking water for three days followed by only 0.75% v/v ethylene glycol for 25 days. Rutin (20 mg/kg body weight) and curcumin (60 mg/kg body weight) were given once daily for 28 days by oral route. After treatment period, calcium and oxalate levels in urine and kidney tissue homogenate were measured. Kidney was also used for histopathological examination. RESULTS: Stone-induction with ethylene glycol and ammonium chloride resulted in elevated levels of calcium and oxalate in the urine and kidney sample, whereas supplementation of rutin and curcumin restored it near to normal. Histopathological study revealed minimum tissue damage and less number of calcium oxalate deposits in kidney of animal treated with rutin and curcumin as compared to calculi-induced animal. CONCLUSION: The data suggest that the rutin and curcumin inhibits calcium oxalate urolithiasis. This effect is mediated possibly through a lowering of urinary concentration of stone forming constituents, anti-inflammatory and antioxidant effects.

Gastroretentive drug delivery of metformin hydrochloride: formulation and in vitro evaluation using 3(2) full factorial design.

Metformin Hydrochloride (MF) is glucose lowering agent that is widely used for management for type II diabetes. MF is reported to be absorbed mainly in upper part of GIT. It is having narrow absorption window and high water solubility, and it would be more beneficial to retain the drug in stomach for prolonged duration so as to achieve maximum absorption and better bioavailability. A conventional oral CR formulation releases most of the drug content at the colon, which requires that the drug will be absorbed from the colon. The present investigation is aimed to develop novel gastroretentive (GR) drug delivery system, which not only release the drug in the absorption window but also provides controlled release drug profile that may result patient compliance and therapeutic success. Floating tablets of MF was prepared using sodium alginate, and sodium carboxymethylcellulose was used as a gelling agent, and release modifiers, respectively. Eudragit NE 30 D was used as sustained release polymer to control the initial burst release. Drug and excipients compatibility studies were monitored by thermal analysis by using differential scanning calorimeter. 32 full factorial design was applied to optimize the formulation. The DSC thermogram of drug, polymer and physical mixtures revealed that there was no known interaction between drug and polymers. The prepared tablets were evaluated for in vitro dissolution, in vitro buoyancy, percentage swelling, percentage erosion and similarity factors with marketed tablets. The optimization study using a 32 full factorial design revealed that the amount of sodium alginate and sodium carboxymethylcellulose had a significant effect on t50, t90, Flag and f2. Thus, by selecting a suitable composition of release rate modifier and gel forming agent, Gastro retentive system can be developed with the desired dissolution profile. This study indicated that the MF GR tablets prepared using sodium alginate and sodium carboxymethylcellulose can successfully be employed as a once-a-day oral controlled release drug delivery system.